Safety Profile of a Modified All-Oral Short-Term Regimen for Drug-Resistant Tuberculosis: an Experimental Assessment
G. N. Mozhokina,
E. R. Pereverzeva,
S. G. Yazeryan,
V. A. Polozkova,
A. E. Shchekotikhin,
A. G. Samoilova https://doi.org/10.58838/2075-1230-2026-104-3-16-25
Abstract
The objective: to evaluate the toxicity of bedaquiline and delamanid combined with linezolid or sutezolid (Szd) in a rat model.
Materials and methods: Rats in the experimental groups (EG) were orally administered Bdq+Dlm+Lzd (EG1) or Bdq+Dlm+Szd (EG2). Rats in the control group (CG) orally received 1% starch gel. For all groups, the administration period lasted 14 days. Subsequently, functional, hematological, biochemical, and pathomorphological tests were conducted, with results compared between the experimental groups and the control group.
Results: Prolongation of QT and RR intervals on ECG and similar signs of toxic cardiomyopathy development were observed in rats of both experimental groups, driven by the effects of delamanid and bedaquiline on the cardiac conduction system. Based on functional and morphological criteria, the hepatotoxic properties of the combination containing sutezolid were less pronounced. Evidence of tubulointerstitial nephritis was detected exclusively in EG1 rats. Hematological changes were similar in both experimental groups and transient in nature; however, granulocytopenia, lymphocytopenia, and thrombocytopenia occurred at earlier stages when linezolid was used.
About the Authors
G. N. Mozhokina
National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of the Russian Federation; Gause Institute of New Antibiotics
Russian Federation
Russian Federation
Galina N. Mozhokina, Doctor of Medical Sciences, Leading Researcher, Research Laboratory of Immunopathology and Immunodiagnostics of Tuberculosis Infection (NMRC PId); Leading Researcher,
Laboratory of Pharmacology and Chemotherapy, Gause
Institute of New Antibiotics
127473, Moscow, 4 Dostoevsky Street, Building 2;
Tel.: +7 (495) 631-15-15;
11 Bolshaya Pirogovskaya St, Moscow, 119021;
Tel. +7 (499) 246-99-80
E. R. Pereverzeva
Gause Institute of New Antibiotics
Russian Federation
Russian Federation
Eleonora R. Pereverzeva, Doctor of Biological Sciences, Chief Researcher, Laboratory of Pharmacology and Chemotherapy
11 Bolshaya Pirogovskaya St, Moscow, 119021;
Tel. +7 (499) 246-99-80
S. G. Yazeryan
Gause Institute of New Antibiotics
Russian Federation
Russian Federation
Sofia G. Yazeryan, Postgraduate student, Laboratory of Pharmacology and Chemotherapy
11 Bolshaya Pirogovskaya St, Moscow, 119021;
Tel. +7 (499) 246-99-80
V. A. Polozkova
Gause Institute of New Antibiotics
Russian Federation
Russian Federation
Vasilisa A. Polozkova, Candidate of Biological Sciences, Researcher, Laboratory of Pharmacology and Chemotherapy
11 Bolshaya Pirogovskaya St, Moscow, 119021;
Tel. +7 (499) 246-99-80
A. E. Shchekotikhin
Gause Institute of New Antibiotics
Russian Federation
Russian Federation
Andrey E. Shchekotikhin, Doctor of Chemical Sciences,
Professor of the Russian Academy of Sciences, Director of the Gause Institute of New Antibiotics
11 Bolshaya Pirogovskaya St, Moscow, 119021;
Tel. +7 (499) 246-99-80
A. G. Samoilova
National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Anastasia G. Samoilova, Doctor of Medical Sciences, Deputy Director for Science
127473, Moscow, 4 Dostoevsky Street, Building 2;
Tel.: +7 (495) 631-15-15
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Review
For citations:
Mozhokina G.N., Pereverzeva E.R., Yazeryan S.G., Polozkova V.A., Shchekotikhin A.E., Samoilova A.G. Safety Profile of a Modified All-Oral Short-Term Regimen for Drug-Resistant Tuberculosis: an Experimental Assessment. Tuberculosis and Lung Diseases. 2026;104(3):16-25. (In Russ.) https://doi.org/10.58838/2075-1230-2026-104-3-16-25
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